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The most frequently used criteria for cognitive impairment in people with HIV are the HIV–associated neurocognitive disorders (HAND) criteria, developed in 2007 by a working group formed by the US National Institute of Mental Health. The HAND criteria (sometimes referred to as the Frascati criteria) were intended for use in research, but the terminology has become widely used to refer to clinical burden of cognitive impairment in people with HIV across diverse settings globally.

Aims: \ud To assess associations of comorbidity patterns observed in people living with HIV (PLWH) with risk factors and health outcomes.\ud \ud Methods: \ud Common patters of comorbidities in PLWH participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study were determined using principal component analysis and a severity score for each pattern was derived. Associations between each pattern's severity score and risk factors were assessed using median regression. The independent associations of patterns’ severity scores with self-reported physical and mental health (SF-36 summary scores) were assessed using linear regression, with functional impairment (Lawton IADL < 8) and hospitalization in last year using logistic regression and with number of general practitioner visits using Poisson regression.\ud \ud Results: \ud A total of 1073 PLWH were analysed: 85.2% male, median (interquartile range) age 52 (47–59) years, 98% on therapy. Duration of HIV was associated with higher severity in 4/6 of patterns: cardiovascular diseases, mental health problems, metabolic disorders and chest/other infections (all P ≤ 0.001). Prior AIDS was associated with higher severity scores for the same patterns and for the pattern of cancers (P < 0.001). The pattern of cardiovascular diseases was associated with poorer physical health (P = 0.02), higher risk of functional impairment (P = 0.02) and hospitalization (P < 0.001) and with higher number of general practitioner visits (P < 0.001). Severity of mental health (all P < 0.001) and of chest/other infections patterns negatively affected all the five health outcomes.\ud \ud Conclusion: \ud Common patterns of comorbidities seen in PLWH appear to have different risk factors and to differently affect health outcomes. These findings may assist the development of targeted intervention to prevent, treat and manage the increasingly prevalent multimorbidity in PLWH.

Background The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach., We have previously described a novel multivariate method (NMM) with theoretical statistical advantages over existing methods, which we assessed here in 3 cohorts of people living with HIV. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status.

Background\ud Bacterial native vertebral osteomyelitis (NVO) can present diagnostic and therapeutic challenges leading to high levels of morbidity and mortality. To inform strategies aimed at improving outcomes in these patients, data are needed on the current aetiology, diagnostic interventions, management and risk factors for treatment failure.\ud \ud Methods\ud This was a retrospective, multicentre, observational cohort study of adult patients with bacterial NVO across the UK between 1st January 2015 and 31st December 2016. Infectious Disease Society of America (IDSA) guideline standards were selected and used to audit practice relating to the management of these patients.\ud \ud Results\ud A total of 286 patients were included from 40 hospitals. An organism was identified in 61% of cases by blood culture or biopsy. Of these, 51% were due to Staphylococcus aureus and 12% were due to Gram-negative bacteria. When performed, biopsy obtained a microbiological diagnosis in 50% of cases. Nearly 10% of patients required admission to an Intensive Care Unit, 20% were re-admitted to hospital, 56% experienced complications and 6% died within 90 days. Higher Charlson comorbidity index (CCI) was significantly associated with treatment failure at one month (p=0.004).\ud \ud Conclusions\ud This study identified opportunities to improve UK practice in the investigation and management of bacterial NVO. The range of organisms isolated supports the use of diagnostic biopsy where blood cultures are non-diagnostic, to guide antimicrobial therapy and strive to avoid treatment failure or complications. This study shows a clear need for antibiotic guidelines to reflect the current aetiology of NVO and authors support the creation of a formal registry.

Objectives\ud\udThe aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH).\ud\ud\udMethods\ud\udPLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into ‘low’ (< 10%), ‘intermediate’ (10–20%) and ‘high’ (> 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland–Altman plots.\ud\udResults\ud\udThe 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49–59] years. The median calculated 10‐year CVD risk was 11.9% (IQR 6.8–18.4%), 8.9% (IQR 4.6–15.0%), 8.5% (IQR 4.8–14.6%) and 6.9% (IQR 4.1–11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50–0.60 range.\ud\ud\udConclusions\ud\udEstimates of predicted 10‐year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone.

Supplemental material, STD881080 Supplemental Material for Cognitive function and drivers of cognitive impairment in a European and a Korean cohort of people living with HIV by Davide De Francesco, Jae-Phil Choi, Jun Y Choi, Rosan A van Zoest, Jonathan Underwood, Judith Schouten, Nam S Ku, Woo J Kim, Peter Reiss, Caroline A Sabin, Alan Winston and On behalf of the ComorBidity in Relation to AIDS (COBRA) Collaboration and the Korean NeuroAIDS Project in International Journal of STD & AIDS

Background The aims of this study were to identify common patterns of comorbidities observed in people living with HIV (PLWH), using a data-driven approach, and evaluate associations between patterns identified. Methods A wide range of comorbidities were assessed in PLWH participating in 2 independent cohorts (POPPY: UK/Ireland; AGEhIV: Netherlands). The presence/absence of each comorbidity was determined using a mix of self-reported medical history, concomitant medications, health care resource use, and laboratory parameters. Principal component analysis (PCA) based on Somers’ D statistic was applied to identify patterns of comorbidities. Results PCA identified 6 patterns among the 1073 POPPY PLWH (85.2% male; median age [interquartile range {IQR}], 52 [47–59] years): cardiovascular diseases (CVDs), sexually transmitted diseases (STDs), mental health problems, cancers, metabolic disorders, chest/other infections. The CVDs pattern was positively associated with cancer (r = .32), metabolic disorder (r = .38), mental health (r = .16), and chest/other infection (r = .17) patterns (all P < .001). The mental health pattern was correlated with all the other patterns (in particular cancers: r = .20; chest/other infections: r = .27; both P < .001). In the 598 AGEhIV PLWH (87.6% male; median age [IQR], 53 [48–59] years), 6 patterns were identified: CVDs, chest/liver, HIV/AIDS events, mental health/neurological problems, STDs, and general health. The general health pattern was correlated with all the other patterns (in particular CVDs: r = .14; chest/liver: r = .15; HIV/AIDS events: r = .31; all P < .001), except STDs (r = –.02; P = .64). Conclusions Comorbidities in PLWH tend to occur in nonrandom patterns, reflecting known pathological mechanisms and shared risk factors, but also suggesting potential previously unknown mechanisms. Their identification may assist in adequately addressing the pathophysiology of increasingly prevalent multimorbidity in PLWH.

Background Despite successful antiretroviral therapy people living with HIV (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function and cognitive impairment. This has raised concerns that PLWH may experience accelerated ageing-related brain pathology. Methods We performed a multi-centre longitudinal study of 134 virologically-suppressed PLWH (median age = 56.0 years) and 79 demographically-similar HIV-negative controls (median age = 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multi-modality neuroimaging (T1-weighted, T2-weighted, diffusion-MRI, resting-state functional-MRI, spectroscopy, arterial spin labelling) at baseline and after two-year follow-up. Group differences in rates of change were assessed using linear mixed effects models. Results 123 PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval = 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking, alcohol use, recreational drug use, blood pressure, body-mass index or cholesterol levels. At baseline, PLWH had poorer global cognitive performance (P0.1). Cognitive performance was stable across the study period in both groups. Conclusions Our finding indicate that when receiving successful treatment, middle-aged PLWH are not at increased risk of accelerated ageing-related brain changes or cognitive decline over two years, when compared to closely-matched HIV-negative controls.

Physical review / A 96(4), 043415 (2017). doi:10.1103/PhysRevA.96.043415, The dynamics following laser-induced molecular photodissociation of gas-phase CH$_{2}$BrI at 271.6 nm were investigated by time-resolved Coulomb-explosion imaging using intense near-IR femtosecond laser pulses. The observed delay-dependent photofragment momenta reveal that CH$_{2}$BrI undergoes C-I cleavage, depositing 65.6% of the available energy into internal product states, and that absorption of a second UV photon breaks the C-Br bond ofCH$_{2}$Br. Simulations confirm that this mechanism is consistent with previous data recorded at 248 nm, demonstrating the sensitivity of Coulomb-explosion imaging as a real-time probe of chemical dynamics., Published by American Physical Society, Woodbury, NY

Background Combination antiretroviral therapy has dramatically improved the outlook for people living with HIV-infection worldwide. As such, the focus of care in well-treated individuals has shifted to the management of long-term comorbidities, such as cognitive impairment. However, the pathogenesis of cognitive impairment in virologically suppressed individuals is unclear. Aims To determine the prevalence, characteristics and understand the pathogenesis of cognitive impairment in well-treated HIV-positive individuals and to assess biomarkers for their ability to predict cognitive impairment and longitudinal changes in cognition. Methods Cross-sectional analysis of two European cohorts (POPPY and COBRA) and longitudinal analysis of the CHARTER cohort using blood, cerebrospinal fluid, clinical, cognitive and neuroimaging data with advanced statistical techniques including machine-learning. Results Firstly, cognitive impairment was prevalent in ~20% of successfully treated patients compared to ~5% in demographically comparable controls. However, it was mild, not clearly associated with symptoms and remained stable over time. Additionally, the prevalence depended on the diagnostic method used, with simulation data demonstrating that the commonly used ‘Frascati criteria’ classifies impairment in ~25-50% of a normative control population. Secondly, cognitive impairment in well-treated patients was predominantly associated with white matter microstructural injury rather than grey or white matter atrophy and using multivariate machine learning techniques could be predicted with up to 80% accuracy. Thirdly, greater exposure to efavirenz and nevirapine were associated with clinical and neuroimaging signals of CNS neurotoxicity. However, these results should be interpreted with caution given their cross-sectional nature and limited sample size (n=60). Nevertheless, they justify further, prospective study given that millions are prescribed these drugs worldwide. Conclusions Cognitive impairment was more prevalent in well-treated HIV-positive patients compared to well matched controls, with white matter microstructural injury sustained before sustained suppression of HIV-viraemia the likely pathogenic driver. Reassuringly however, this impairment was generally mild, asymptomatic and remains stable over time. Open Access

Cognitive tests administered by cognitive domain. (DOCX 13 kb)

This review article discusses advances in the use of time-resolved photoelectron spectroscopy for the study of non-adiabatic processes in molecules. A theoretical treatment of the experiments is presented together with a number of experimental examples., Comment: 84 pages, 33 figures

We present a definition of the non-abelian generalisations of affine Toda theory related from the outset to vertex operator constructions of the corresponding Kac-Moody algebra $\gh$. Reuslts concerning conjugacy classes of the Weyl group of the finite Lie algebra $\fing$ to embeddings of $A_1$ in $\fing$ are used both to present the theories, and to elucidate their soliton spectrum. We confirm the conjecture of \cite{OSU93} for the soliton specialisation of the Leznov-Saveliev solution. The energy-momentum tensor of such theories is shown to split into a total derivative part and a part dependent only on the free fields which appear in the general solution, and vanish for the soliton solutions. Analogues are provided of the results known for the classical solitons of abelian Toda theories., Comment: 29 pages, Imperial/TP/92-93/30

We provide a proof of a formula conjectured in \cite{OU93} for some coefficients relevant in the principal vertex operator construction of a simply-laced affine algebra $\gh$. These coefficients are important for the study of the topological charges of the solitons of affine Toda theories, and the construction of representations of non-simply-laced $\gh$ and their associated Toda solitons., Comment: 6 pages, Imperial/TP/92-93/38

Accelerator based Ultrafast Electron Diffraction (UED) is a technique for obtaining static structures and for studying sub-100 fs dynamic structural changes on the atomic scale. In this paper we present the first electron diffraction results obtained from the VELA accelerator in 2014. The accelerator was operated to provide typically 4MeV/c electron bunches. Diffraction patterns were observed with <, Proceedings of the 6th Int. Particle Accelerator Conf., IPAC2015, Richmond, VA, USA